الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Cancer colon (CC) is a gastrointestinal malignancy seriously affecting human health, globally it represents the fourth in terms of incidence and the third in mortality rates, also It is the most common cancer of the gastrointestinal system. Early diagnosis and treatment is the key. Surgical resection is the most effective treatment. However, many patients are diagnosed in the advanced stage therefore do not have the chance to undergo surgical treatment, mostly due to lack of clinical manifestations at the early stage, and no evidence of specific screening method. Therefore, an effective method for early detection of CC is needed, e.g. miRNAs.
The miRNAs are a group of short non-coding RNAs which repress protein translation by binding to their target mRNAs. Cloning studies and bioinformatics reported that miRNAs may regulate 30% of all human genes and control hundreds of gene targets. Globally abnormal miRNA expression can classify human cancers, detects their progression, invasion, and response to therapy. It was well-documented that certain miRNAs contribute to cell proliferation, transformation, and tumorigenesis through acting as targets of genomic lesions which are associated with either activation of oncogenes or inactivation of tumor suppressor genes in cancer cells. Furthermore, many studies have revealed the pro and anti-tumorigenic activities of specific miRNAs both in vitro and in vivo.
The miRNA-31 is an important regulator of immune system function, embryonic implantation, development and muscle or bone homeostasis. MiRNA-31 expression level is altered in many cancers; it is increased in squamous cell carcinoma, head and neck cancer and hepatocellular carcinoma, but significantly decreased in gastric, breast, urothelial and prostate cancer. Furthermore, previous research revealed that on certain occasions, miR-31 can act as either a tumor suppressor or an oncogenic miRNA. MicroRNA-141 is an important member of the miR-200 family that is composed of five members. Dysregulated miRNA-141 has been demonstrated in many types of cancers. It regulates different cellular processes, such as proliferation, migration, angiogenesis, epithelial mesenchymal transition, chemosensitivity and apoptosis by modulating multiple targets. Dysregulation of miR-141 depends on the cancer type. MiR-141 acts a dual role in tumorigenicity, also it can modulate cellular motility. MiR-141 was found to be upregulated in various cancers such as ovarian, lung, colorectal, nasopharyngeal, bladder and prostate cancers, in these cancers miR-141 acts as oncogene. However, it exerts a tumor suppressive effect on other types of cancer and hence it is down-regulated in gastric, breast, pancreatic cancers, hepatocellular and primary peritoneal carcinoma.
The aim of the present work was to determine the tissue and serum expression of miR-31 and miR-141 in Egyptian patients with CC and to study their possible association with the different clinicopathological features.
Fifty subjects were enrolled in this study. They were divided into 2 groups; patients group: 25 newly diagnosed stage II and III primary cancer colon patients, and control group: 25 healthy controls as proven by colonoscopy or CT scan. Three milliliters of whole venous blood samples were withdrawn from both groups under aseptic technique. Multiple fresh punched biopsies were taken from cancer colon patients from both cancerous and non-
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cancerous colon tissues after leaving at least 15 cm as a safety margin. RNA extraction was done using silica gel technique. Quantitative real time PCR was done after conversion of RNA into cDNA using taqman probe. Relative expressions of both miRNAs were calculated by comparative cycle threshold method (2–ΔΔCT).
The present study showed a statistically significant increase in expression of miRNA-31 in cancerous tissues more than adjacent noncancerous tissues. A ROC curve analysis for tissue miRNA-31 expression in cancer colon, generated a cut off value of (>0.867) with AUC of 0.757 that was sufficient to detect the presence of cancer colon with diagnostic sensitivity of 84% and diagnostic specificity of 60%. However, there was no statistically significant difference in the expression of miR-31 in the serum between cancer colon patients and control group.
Regarding miRNA-141; there was a statistically significant increase in serum miRNA-141 in cancer colon patients more than the control group. A ROC curve showed that AUC for serum miRNA-141 was 0.869. A cut off value of (≥3.4388) was sufficient to detect the presence of cancer colon with diagnostic sensitivity of 80% and specificity of 92%. However, there was no statistically significant difference in miRNA-141 expression between cancerous and adjacent noncancerous tissues of cancer colon patients.
In conclusion, the significantly upregulated tissue miRNA-31 in cancerous more than adjacent noncancerous tissues and the upregulation of serum miRNA-141 in cancer colon patients more than control group could support their use in diagnosis and their possible role in tumerogenesis of cancer colon. In addition, serum miR-141 could be used as non-invasive molecular biomarker for early diagnosis of CC. However further studies of these miRNAs on a larger scale are highly warranted.
This study had a limitation of its small sample size. However it also had points of strength that it was conducted on cancer colon only not including rectum, while most of other studies were performed on colorectal cancer. Another point of strength is that it studied miRNA-31 and miRNA-141 expression in both tissues and serum of the same